Extracting uranium from wastewater is highly essential for addressing environmental pollution and sustainable development of nuclear power. However, the design and synthesis of functional adsorbents for selective and rapid uranium adsorption remains extremely challenging. Herein, we report the synthesis of a functionalized hyper-cross-linked polymers (PHCP-Q) via an interfacial and coordination microenvironment synergistic modulation strategy for efficient uranium adsorption. The generated interfacial hydrophilic microenvironment allows the rapid migration of uranyl from the solution to the adsorbent and thus enables fast adsorption kinetics. Meanwhile, the fine-tuned coordination microenvironment within pore space creates the hexa-coordinated nano-pocket structure and thereby enhances the selective recognition of uranyl. Remarkably, PHCP-Q achieves adsorption equilibrium within simply 60 min and shows high saturation U(VI) adsorption uptake of 608.95 mg/g. More importantly, PHCP-Q with the cooperation of binding sites exhibits the highest distribution coefficient by an order of magnitude compared with that of other PHCPs. Besides, PHCP-Q possesses good physicochemical stability and recyclability. This study provides a new insight into the future design of highly effective uranium adsorbents by synergistically modulating interfacial and coordination microenvironment, which can be extended to the extraction of other target ions.